Brainstem Control of Subcortical Visual Information

描述(申请人提供)：膝状体背外侧核 (LGN)是感知链中至关重要的一环。视网膜神经节细胞编码 视觉世界并将其传输到LGN。大多数人都同意，这一门槛 信息发生在视网膜起源的突触，但一个完整的机制是 难以捉摸。我们最近的发现证明了几个新的和令人兴奋的来源 在LGN的视觉信息的动态控制。其中两个是已知的 中继神经元的调节物：胆碱能臂旁脑干(PBR)和 大量皮质激素(CG)反馈。PBR释放一氧化氮 (不)，我们的数据表明，NO影响视网膜的方式有惊人的不同 和大脑皮层输入。NO具有很强的选择性抑制作用。 通过与NMDA的相互作用在LGN中进行视黄素化传递 然而，通过CG途径的传递被增强了两个 不同的机制。关于丘脑功能的另一大谜团是 从第6层到LGN的皮质反馈的目的，我们现在看到的是 与PBR和NO密切相关。我们提出了一系列新的实验 为了揭示PBR的贡献和大脑皮层反馈的影响， 一种全球假说，即视觉需要两者的合作活动模式 这些小路中。目的1：一氧化氮如何影响LGN继发细胞膜 房产？NO抑制视黄醇原核NMDA受体功能 路径。我们假设NO也以低阈值钙电流为靶标 (I(T))和关键K+电流(I)(AS))。我们将对I(T)和I(AS)进行调查 来自LGN切片的细胞内贴片记录，而不提供 供体和清道夫，并通过刺激内源性NO的产生 酶bnos。目的2：NO如何影响LGN中继细胞的快速突触输入？ 我们将刺激视网膜和CG通路(以激发GABA能IPSP/JPSCs) 和CG途径(以激发谷氨酸能EPSP/EPSCs)，而 不操纵任何关卡。我们假设NO的影响方式截然不同 视网膜和皮质EPSP/EPSCs；皮质EPSP/EPSCs增强，提示 PBR可能通过NO改变视网膜前馈的平衡 并朝着皮质反馈处理的方向发展。目标3：如何 皮质膝状体投射控制丘脑皮质对话？中继室 以两种模式之一对视网膜输入做出反应，爆裂或紧张性。我们假设 第6层促进了爆发和紧张性反应的视觉梯度，并且 同步发射，在LGN。我们将录制来自丘脑合唱团的节目 视觉处理，在激活和失活视觉皮质第六层的同时， 在激活脑干通路的同时。视网膜输入对LGN的影响是 众所周知，但该领域正在努力解决 视网膜外突触的影响。这些问题的答案将是 完全改变了我们对丘脑功能的看法，而不是 在将视觉的线捆绑在一起时，将周边与皮质结合在一起的伙伴 感知力。

DESCRIPTION (provided by applicant): The dorsal lateral geniculate nucleus (LGN) is a vital link in the chain of perception. Retinal ganglion cells encode the visual world and transmit it to the LGN. Most agree that gating of this information occurs at the retinogeniculate synapse, but a complete mechanism is elusive. Our recent findings demonstrate several new and exciting sources of dynamic control of visual information at the LGN. Two of these are known modulators of relay neurons: the cholinergic parabrachial brainstem (PBR) and the massive corticogeniculate (CG) feedback. The PBR releases nitric oxide (NO), and our data indicate an amazing difference in the way NO affects retinal and cortical inputs. NO has a powerful and selective inhibitory influence on retinogeniculate transmission in the LGN through interaction with the NMDA receptor; however, transmission through the CG pathway is enhanced by two separate mechanisms. The other great remaining mystery of thalamic function is the purpose of the cortical feedback to LGN from layer 6, which we now see as intimately linked with the PBR and NO. We propose a new series of experiments to reveal the contributions of the PBR, and cortical feedback influences, with a global hypothesis that vision requires cooperative activity patterns of both of these pathways. Aim 1: How does NO affect LGN relay cell membrane properties? NO suppresses NMDA receptor function in the retinogeniculate pathway. We hypothesize that NO also targets the low threshold Ca2+ current (I(T)) and a key K+ currents (I) (As)). We will probe I(T) and I(As) with intracellular patch recordings from slices of the LGN, while delivering NO donors and scavengers, and by stimulating intrinsic NO production through the enzyme bNOS. Aim 2: How does NO affect fast synaptic inputs to LGN relay cells? We will stimulate the retinal and CG pathways (to evoke GABAergic IPSP/JPSCs) and the CG pathway (to evoke glutamatergic EPSP/EPSCs) in slices while manipulating NO levels. We hypothesize a stark difference in how NO affects retinal and cortical EPSP/EPSCs; cortical EPSP/EPSCs are enhanced, indicating that the PBR, through NO, may shift the balance away from retinal feedforward processing and toward cortical feedback processing. Aim 3: How does the corticogeniculate projection control the thalamocortical dialog? Relay cells respond to retinal inputs in one of two modes, burst or tonic. We hypothesize that layer 6 promotes a visuotopic gradient of burst and tonic responses, and synchronous firing, in the LGN. We will record from thalamic ensembles during visual processing, while activating and inactivating layer 6 of visual cortex, and while activating brainstem pathways. The impact of retinal inputs to LGN is well known, but the field is struggling with the nature and scope of extraretinal synaptic influences. The answers to these questions will completely transform our view of thalamic function from that of a slave of the periphery to a partner with cortex in binding together the threads of visual perception.